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1.
Front Pharmacol ; 15: 1414790, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39246660

RESUMEN

Cancer prevention is currently envisioned as a molecular-based approach to prevent carcinogenesis in pre-cancerous stages, i.e., dysplasia and carcinoma in situ. Cancer is the second-leading cause of mortality worldwide, and a more than 61% increase is expected by 2040. A detailed exploration of cancer progression pathways, including the NF-kß signaling pathway, Wnt-B catenin signaling pathway, JAK-STAT pathway, TNF-α-mediated pathway, MAPK/mTOR pathway, and apoptotic and angiogenic pathways and effector molecules involved in cancer development, has been discussed in the manuscript. Critical evaluation of these effector molecules through molecular approaches using phytomolecules can intersect cancer formation and its metastasis. Manipulation of effector molecules like NF-kß, SOCS, ß-catenin, BAX, BAK, VEGF, STAT, Bcl2, p53, caspases, and CDKs has played an important role in inhibiting tumor growth and its spread. Plant-derived secondary metabolites obtained from natural sources have been extensively studied for their cancer-preventing potential in the last few decades. Eugenol, anethole, capsaicin, sanguinarine, EGCG, 6-gingerol, and resveratrol are some examples of such interesting lead molecules and are mentioned in the manuscript. This work is an attempt to put forward a comprehensive approach to understanding cancer progression pathways and their management using effector herbal molecules. The role of different plant metabolites and their chronic toxicity profiling in modulating cancer development pathways has also been highlighted.

2.
BMJ Case Rep ; 17(9)2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39284683

RESUMEN

The follow-up of teeth that have undergone regenerative endodontic procedures through radiographic imaging is crucial for evaluating their success and determining their future prognosis. The periapical radiographs stand out as the primary tool for this task and are also recommended by the existing guidelines. However, two-dimensional (2D) imaging may not reveal the findings accurately, mimicking the root formation success which may not be true otherwise when assessed using cone beam CT (CBCT) imaging. This case series featuring two instances underscores the significance of CBCT in identifying such signs of failure, particularly when they might be obscured in 2D imaging.


Asunto(s)
Tomografía Computarizada de Haz Cónico , Imagenología Tridimensional , Endodoncia Regenerativa , Raíz del Diente , Humanos , Tomografía Computarizada de Haz Cónico/métodos , Raíz del Diente/diagnóstico por imagen , Endodoncia Regenerativa/métodos , Masculino , Femenino , Adulto , Tratamiento del Conducto Radicular/métodos
3.
Sci Rep ; 14(1): 20711, 2024 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-39237689

RESUMEN

Tuberculosis (TB) is the leading cause of mortality among infectious diseases globally. Effectively managing TB requires early identification of individuals with TB disease. Resource-constrained settings often lack skilled professionals for interpreting chest X-rays (CXRs) used in TB diagnosis. To address this challenge, we developed "DecXpert" a novel Computer-Aided Detection (CAD) software solution based on deep neural networks for early TB diagnosis from CXRs, aiming to detect subtle abnormalities that may be overlooked by human interpretation alone. This study was conducted on the largest cohort size to date, where the performance of a CAD software (DecXpert version 1.4) was validated against the gold standard molecular diagnostic technique, GeneXpert MTB/RIF, analyzing data from 4363 individuals across 12 primary health care centers and one tertiary hospital in North India. DecXpert demonstrated 88% sensitivity (95% CI 0.85-0.93) and 85% specificity (95% CI 0.82-0.91) for active TB detection. Incorporating demographics, DecXpert achieved an area under the curve of 0.91 (95% CI 0.88-0.94), indicating robust diagnostic performance. Our findings establish DecXpert's potential as an accurate, efficient AI solution for early identification of active TB cases. Deployed as a screening tool in resource-limited settings, DecXpert could enable early identification of individuals with TB disease and facilitate effective TB management where skilled radiological interpretation is limited.


Asunto(s)
Programas Informáticos , Humanos , India/epidemiología , Femenino , Masculino , Adulto , Persona de Mediana Edad , Diagnóstico por Computador/métodos , Tuberculosis/diagnóstico , Tuberculosis/diagnóstico por imagen , Tuberculosis Pulmonar/diagnóstico por imagen , Tuberculosis Pulmonar/diagnóstico , Sensibilidad y Especificidad , Adulto Joven , Adolescente , Radiografía Torácica/métodos , Anciano
4.
Sci Rep ; 14(1): 20404, 2024 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-39223248

RESUMEN

The research introduces a novel method for creating drug-loaded hydrogel beads that target anti-aging, anti-oxidative, and anti-inflammatory effects, addressing the interconnected processes underlying various pathological conditions. The study focuses on the development of hydrogel beads containing anti-aging compounds, antioxidants, and anti-inflammatory drugs to effectively mitigate various processes. The synthesis, characterization and in vitro evaluations, and potential applications of these multifunctional hydrogel beads are discussed. A polymeric alginate-orange peel extract (1:1) hydrogel was synthesized for encapsulating fish oil. Beads prepared with variable fish oil concentrations (0.1, 0.3, and 0.5 ml) were characterized, showing no significant decrease in size i.e., 0.5 mm and a reduction in pore size from 23 to 12 µm. Encapsulation efficiency reached up to 98% within 2 min, with controlled release achieved upto 45 to 120 min with increasing oil concentration, indicating potential for sustained delivery. Fourier-transform infrared spectroscopy confirmed successful encapsulation by revealing peak shifting, interaction between constituents. In vitro degradation studies showed the hydrogel's biodegradability improved from 30 to 120 min, alongside anti-inflammatory, anti-oxidative, anti-collagenase and anti-elastase activities, cell proliferation rate enhanced after entrapping fish oil. In conclusion, the synthesized hydrogel beads are a promising drug delivery vehicle because they provide stable and effective oil encapsulation with controlled release for notable anti-aging and regenerative potential. Targeted delivery for inflammatory and oxidative stress-related illnesses is one set of potential uses. Further research may optimize this system for broader applications in drug delivery and tissue engineering.


Asunto(s)
Alginatos , Antioxidantes , Aceites de Pescado , Hidrogeles , Alginatos/química , Aceites de Pescado/química , Hidrogeles/química , Antioxidantes/farmacología , Antioxidantes/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Humanos , Envejecimiento/efectos de los fármacos , Animales , Extractos Vegetales/química , Extractos Vegetales/farmacología , Microesferas , Ratones
5.
Front Pharmacol ; 15: 1403900, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39135797

RESUMEN

Pantothenate synthetase protein plays a pivotal role in the biosynthesis of coenzyme A (CoA), which is a crucial molecule involved in a number of cellular processes including the metabolism of fatty acid, energy production, and the synthesis of various biomolecules, which is necessary for the survival of Mycobacterium tuberculosis (Mtb). Therefore, inhibiting this protein could disrupt CoA synthesis, leading to the impairment of vital metabolic processes within the bacterium, ultimately inhibiting its growth and survival. This study employed molecular docking, structure-based virtual screening, and molecular dynamics (MD) simulation to identify promising phytochemical compounds targeting pantothenate synthetase for tuberculosis (TB) treatment. Among 239 compounds, the top three (rutin, sesamin, and catechin gallate) were selected, with binding energy values ranging from -11 to -10.3 kcal/mol, and the selected complexes showed RMSD (<3 Å) for 100 ns MD simulation time. Furthermore, molecular mechanics generalized Born surface area (MM/GBSA) binding free energy calculations affirmed the stability of these three selected phytochemicals with binding energy ranges from -82.24 ± 9.35 to -66.83 ± 4.5 kcal/mol. Hence, these identified natural plant-derived compounds as potential inhibitors of pantothenate synthetase could be used to inhibit TB infection in humans.

6.
Rheumatol Int ; 2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39180530

RESUMEN

To look for the spectrum of infections and the factors predisposing to infection in patients with systemic sclerosis (SSc). In this retrospective study, demographic, clinical features, details of infections, immunosuppressive therapy, and outcomes of patients with SSc attending clinics at department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India from 1990 to 2022 were captured. Multivariable-adjusted logistic regression was applied to identify independent predictors of infection. Data of 880 patients, mean age 35.5 ± 12 years, and female: male ratio 7.7:1, were analyzed. One hundred and fifty-three patients had at least 1 infection with a total of 233 infectious episodes. Infections were most common in lung followed by skin and soft tissue. Tuberculosis was diagnosed in 45 patients (29.4%). Klebsiella was the commonest non-tubercular organism in lung and Escherichia coli in urinary tract infections. In comparison to matched control group, patients with infection had a greater number of admissions due to active disease, odds ratio (OR) 6.27 (CI 3.23-12.18), were receiving immunosuppressive medication OR, 5.05 (CI 2.55-10.00), and had more digital ulcers OR, 2.53 (CI 1.17-5.45). Patients who had infection had more likelihood for death OR, 13.63 (CI 4.75 -39.18). Tuberculosis is the commonest infection and lung remains the major site of infection in patients with SSc. Number of hospital admissions, digital ulcers and immunosuppressive therapy are predictors of serious infection in patients with SSc. Patients with infections had more likelihood of death.

7.
Cureus ; 16(7): e64831, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39156345

RESUMEN

Introduction Medical science must be based on sound and scientific evidence and requires continuous research. Engaging in research allows students and faculty to explore new frontiers, question existing paradigms, and discover innovative solutions to medical challenges. As a specialty, community medicine plays a pivotal role in addressing public health issues. However, the engagement of community medicine residents in biomedical research remains suboptimal, which may impede the generation of evidence-based practices tailored to the Indian context. This study was conducted to find the interest and engagement of community medicine residents, and factors influencing their interest in biomedical research. Methods An online survey was conducted among community medicine residents of Uttar Pradesh, from February to April 2024, using Google Forms having a semi-structured, pretested questionnaire. Results One hundred and ninety-six residents participated in the study, where females (52.6%; 103/196) outnumbered males (47.4%; 93/196). The majority of participants were third-year residents (40.8%). Most participants seemed interested in biomedical research (83.2%) and thought that Basic Course in Biomedical Research (BCBR) helps conduct research projects (75%). Around half had previous experience in research projects, with cross-sectional studies being the most common (75.9%) study design. Enhancing research skills and a desire to contribute to medical knowledge emerged as primary motivators. On the other hand, the lack of time due to being overburdened with academic and educational activities was seen as the most common barrier to conducting research. Conclusions The majority of participants were found interested in research activities. The opportunity to improve research skills, desire to serve the medical fraternity, and a positive impact on resumes were the leading motivating factors for conducting research. Difficulty in sparing time, little knowledge, and poor support from mentors were found as important barriers.

8.
Mater Today Bio ; 27: 101139, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39027679

RESUMEN

The prevalence of polymer usage in everyday activities has emerged as a detriment to both human life and the environment. A large number of studies describe severe impacts of micropolymers (MP) and nanopolymers (NP) on various organ systems, including the endocrine system. Additionally, plasticizers utilized as additives have been identified as endocrine-disrupting chemicals (EDCs). MP/NP, along with associated plasticizers, affect principal signalling pathways of endocrine glands such as the pituitary, thyroid, adrenal, and gonads, thereby disrupting hormone function and metabolic processes crucial for maintaining homeostasis, fertility, neural development, and fetal growth. This review delves into the sources, distribution, and effects of micropolymers, nanopolymers, and associated plasticizers acting as EDCs. Furthermore, it provides a detailed review of the mechanisms underlying endocrine disruption in relation to different types of MP/NP.

9.
Mucosal Immunol ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38992433

RESUMEN

The prevalence of obesity in the United States has continued to increase over the past several decades. Understanding how diet-induced obesity modulates mucosal immunity is of clinical relevance. We previously showed that consumption of a high fat, high sugar "Western" diet (WD) reduces the density and function of small intestinal Paneth cells, a small intestinal epithelial cell type with innate immune function. We hypothesized that obesity could also result in repressed gut adaptive immunity. Using small intestinal intraepithelial lymphocytes (IEL) as a readout, we found that in non-inflammatory bowel disease (IBD) subjects, high body mass index correlated with reduced IEL density. We recapitulated this in wild type (WT) mice fed with WD. A 4-week WD consumption was able to reduce IEL but not splenic, blood, or bone marrow lymphocytes, and the effect was reversible after another 2 weeks of standard diet (SD) washout. Importantly, WD-associated IEL reduction was not dependent on the presence of gut microbiota, as WD-fed germ-free mice also showed IEL reduction. We further found that WD-mediated Farnesoid X Receptor (FXR) activation in the gut triggered IEL reduction, and this was partially mediated by intestinal phagocytes. Activated FXR signaling stimulated phagocytes to secrete type I IFN, and inhibition of either FXR or type I IFN signaling within the phagocytes prevented WD-mediated IEL loss. Therefore, WD consumption represses both innate and adaptive immunity in the gut. These findings have significant clinical implications in the understanding of how diet modulates mucosal immunity.

10.
bioRxiv ; 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38979159

RESUMEN

Multiple Myeloma (MM) is a highly prevalent and incurable form of cancer that arises from malignant plasma cells, with over 35,000 new cases diagnosed annually in the United States. While there are a growing number of approved therapies, MM remains incurable and nearly all patients will relapse and exhaust all available treatment options. Mechanisms for disease progression are unclear and in particular, little is known regarding the role of long non-coding RNAs (lncRNA) in mediating disease progression and response to treatment. In this study, we used transcriptome sequencing to compare newly diagnosed MM patients who had short progression-free survival (PFS) to standard first-line treatment (PFS < 24 months) to patients who had prolonged PFS (PFS > 24 months). We identified 157 differentially upregulated lncRNAs with short PFS and focused our efforts on characterizing the most upregulated lncRNA, LINC01432. We investigated LINC01432 overexpression and CRISPR/Cas9 knockdown in MM cell lines to show that LINC01432 overexpression significantly increases cell viability and reduces apoptosis, while knockdown significantly reduces viability and increases apoptosis, supporting the clinical relevance of this lncRNA. Next, we used individual-nucleotide resolution cross-linking immunoprecipitation with RT-qPCR to show that LINC01432 directly interacts with the RNA binding protein, CELF2. Lastly, we showed that LINC01432-targeted locked nucleic acid antisense oligonucleotides reduce viability and increases apoptosis. In summary, this fundamental study identified lncRNAs associated with short PFS to standard NDMM treatment and further characterized LINC01432, which inhibits apoptosis.

11.
Drug Discov Today ; 29(9): 104105, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39029869

RESUMEN

Cancer, a multifaceted and pernicious disease, continuously challenges medicine, requiring innovative treatments. Brain cancers pose unique and daunting challenges due to the intricacies of the central nervous system and the blood-brain barrier. In this era of precision medicine, the convergence of neurology, oncology, and cutting-edge technology has given birth to a promising avenue - targeted cancer therapy. Furthermore, bioinspired microrobots have emerged as an ingenious approach to drug delivery, enabling precision and control in cancer treatment. This Keynote review explores the intricate web of neurological insights into brain-targeted cancer therapy and the paradigm-shifting world of bioinspired microrobots. It serves as a critical and comprehensive overview of these evolving fields, aiming to underscore their integration and potential for revolutionary cancer treatments.


Asunto(s)
Barrera Hematoencefálica , Neoplasias Encefálicas , Sistemas de Liberación de Medicamentos , Medicina de Precisión , Robótica , Humanos , Neoplasias Encefálicas/tratamiento farmacológico , Sistemas de Liberación de Medicamentos/métodos , Barrera Hematoencefálica/metabolismo , Medicina de Precisión/métodos , Animales , Antineoplásicos , Encéfalo/metabolismo
12.
Cancers (Basel) ; 16(12)2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38927885

RESUMEN

Pancreatic cancer is a prevalent lethal gastrointestinal cancer that generally does not show any symptoms until it reaches advanced stages, resulting in a high mortality rate. People at high risk, such as those with a family history or chronic pancreatitis, do not have a universally accepted screening protocol. Chemotherapy and radiotherapy demonstrate limited effectiveness in the management of pancreatic cancer, emphasizing the urgent need for innovative therapeutic strategies. Recent studies indicated that the complex interaction among pancreatic cancer cells within the dynamic microenvironment, comprising the extracellular matrix, cancer-associated cells, and diverse immune cells, intricately regulates the biological characteristics of the disease. Additionally, mounting evidence suggests that EVs play a crucial role as mediators in intercellular communication by the transportation of different biomolecules, such as miRNA, proteins, DNA, mRNA, and lipids, between heterogeneous cell subpopulations. This communication mediated by EVs significantly impacts multiple aspects of pancreatic cancer pathogenesis, including proliferation, angiogenesis, metastasis, and resistance to therapy. In this review, we delve into the pivotal role of EV-associated miRNAs in the progression, metastasis, and development of drug resistance in pancreatic cancer as well as their therapeutic potential as biomarkers and drug-delivery mechanisms for the management of pancreatic cancer.

13.
Front Cell Infect Microbiol ; 14: 1391288, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38919703

RESUMEN

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, is a highly contagious respiratory disease with widespread societal impact. The symptoms range from cough, fever, and pneumonia to complications affecting various organs, including the heart, kidneys, and nervous system. Despite various ongoing efforts, no effective drug has been developed to stop the spread of the virus. Although various types of medications used to treat bacterial and viral diseases have previously been employed to treat COVID-19 patients, their side effects have also been observed. The way SARS-CoV-2 infects the human body is very specific, as its spike protein plays an important role. The S subunit of virus spike protein cleaved by human proteases, such as furin protein, is an initial and important step for its internalization into a human host. Keeping this context, we attempted to inhibit the furin using phytochemicals that could produce minimal side effects. For this, we screened 408 natural phytochemicals from various plants having antiviral properties, against furin protein, and molecular docking and dynamics simulations were performed. Based on the binding score, the top three compounds (robustaflavone, withanolide, and amentoflavone) were selected for further validation. MM/GBSA energy calculations revealed that withanolide has the lowest binding energy of -57.2 kcal/mol followed by robustaflavone and amentoflavone with a binding energy of -45.2 kcal/mol and -39.68 kcal/mol, respectively. Additionally, ADME analysis showed drug-like properties for these three lead compounds. Hence, these natural compounds robustaflavone, withanolide, and amentoflavone, may have therapeutic potential for the management of SARS-CoV-2 by targeting furin.


Asunto(s)
Antivirales , Tratamiento Farmacológico de COVID-19 , Furina , Simulación del Acoplamiento Molecular , Fitoquímicos , SARS-CoV-2 , Furina/antagonistas & inhibidores , Furina/metabolismo , Fitoquímicos/farmacología , Fitoquímicos/química , Humanos , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/enzimología , Antivirales/farmacología , Antivirales/química , Inhibidores de Proteasas/farmacología , Inhibidores de Proteasas/química , Glicoproteína de la Espiga del Coronavirus/metabolismo , Glicoproteína de la Espiga del Coronavirus/antagonistas & inhibidores , Glicoproteína de la Espiga del Coronavirus/química , COVID-19/virología , Unión Proteica
14.
Biomed Pharmacother ; 176: 116921, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38870628

RESUMEN

Pulp therapy has been emerged as a one of the efficient therapies in the field of endodontics. Among different types of new endodontic materials, pulpotec has been materialized as a recognized material for vital pulp therapy. However, its efficacy has been challenged due to lack of information about its cellular biocompatibility. This study evaluates the mechanistic biocompatibility of pulpotec cement with macrophage cells (RAW 264.7) at cellular and molecular level. The biocompatibility was evaluated using experimental and computational techniques like MTT assay, oxidative stress analysis and apoptosis analysis through flow cytometry and fluorescent microscopy. The results showed concentration-dependent cytotoxicity of pulpotec cement extract to RAW 264.7 cells with an LC 50 of X/10-X/20. The computational analysis depicted the molecular interaction of pulpotec cement extract components with metabolic proteins like Sod1 and p53. The study revealed the effects of Pulpotec cement's extract, showing a concentration-dependent induction of oxidative stress and apoptosis. These effects were due to influential structural and functional abnormalities in the Sod1 and p53 proteins, caused by their molecular interaction with internalized components of Pulpotec cement. The study provided a detailed view on the utility of Pulpotec in endodontic applications, highlighting its biomedical aspects.


Asunto(s)
Apoptosis , Materiales Biocompatibles , Macrófagos , Estrés Oxidativo , Estrés Oxidativo/efectos de los fármacos , Apoptosis/efectos de los fármacos , Ratones , Animales , Células RAW 264.7 , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Materiales Biocompatibles/farmacología , Ensayo de Materiales , Supervivencia Celular/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismo , Cementos Dentales/farmacología , Cementos Dentales/química , Superóxido Dismutasa-1/metabolismo
15.
Immunol Res ; 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38879717

RESUMEN

Adjuvants were used to modulate response towards relevant immune cells. The present study aims to investigate FlaA-conjugated Per a 10 and T cell peptides in amelioration of allergic airway disease in mice. Mice given Per a 10 showed allergic features with higher cellular infiltration, IgE, Th-2 cytokines and alarmins. Fusion protein treatment reduced lung inflammation (p < 0.0001) and cellular infiltrates (p < 0.001) with higher IgG2a/IgE indicating resolution of disease. Immunotherapy with FPT1 and FPT3 reduces IL-4, IL-5 and IL-13 levels (p < 0.0001) with a fourfold increase in IFN-γ secretion in BALF. FPT1- and FPT3-treated mice have increased IL-10 and TGF-ß levels (p < 0.001) with CD4+Foxp3+ T cells (p < 0.01) indicating Treg response. There was enhanced expression of claudin-1 (1.7-fold) and occludin (fourfold) in lungs of FPT1- and FPT3-treated mice with reduced TSLP (p < 0.01) and IL-33 (p < 0.0001) secretion in BALF indicating recovery of epithelial function. Peptide-conjugated FlaA proteins showed protective immunity in mice and have potential for immunotherapy with restoration of cellular function.

16.
Mol Neurobiol ; 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38780722

RESUMEN

Plants and their derived phytochemicals have a long history of treating a wide range of illnesses for several decades. They are believed to be the origin of a diverse array of medicinal compounds. One of the compounds found in kudzu root is puerarin, a isoflavone glycoside commonly used as an alternative medicine to treat various diseases. From a biological perspective, puerarin can be described as a white needle crystal with the chemical name of 7-hydroxy-3-(4-hydroxyphenyl)-1-benzopyran-4-one-8-D-glucopyranoside. Besides, puerarin is sparingly soluble in water and produces no color or light yellow solution. Multiple experimental and clinical studies have confirmed the significant therapeutic effects of puerarin. These effects span a wide range of pharmacological effects, including neuroprotection, hepatoprotection, cardioprotection, immunomodulation, anticancer properties, anti-diabetic properties, anti-osteoporosis properties, and more. Puerarin achieves these effects by interacting with various cellular and molecular pathways, such as MAPK, AMPK, NF-κB, mTOR, ß-catenin, and PKB/Akt, as well as different receptors, enzymes, and growth factors. The current review highlights the molecular mechanism of puerarin as a neuroprotective agent in the treatment of various neurodegenerative and neurological diseases. Extensive cellular, animal, and clinical research has provided valuable insights into its effectiveness in conditions such as Alzheimer's disease, Parkinson's disease, epilepsy, cerebral stroke, depression, and more.

17.
Lung India ; 41(2): 130-134, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38700407

RESUMEN

ABSTRACT: A 15-year-old boy presented with a sudden onset of breathlessness for 7 days, gradual loss of weight of 17.6 lbs over the last month and progressive hoarseness of voice for 7 months. The contrast-enhanced computed tomography (CECT) scan revealed a heterogeneously enhancing lesion in the anterior mediastinum with multiple discrete lymph nodes in the cervical and mediastinal locations. The GeneXpert MTB/RIF assay performed on the CT-guided biopsy of the mass was negative, but the culture for Mycobacterium tuberculosis was positive at 7 weeks of incubation. There was a suboptimal radiological response after 6 months of treatment. First-line drug susceptibility testing (DST) performed by line probe assay (LPA) on the positive culture detected high-level resistance to isoniazid. The treatment was modified as per DST results to which the patient responded well.

18.
Biomed Pharmacother ; 176: 116842, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38810404

RESUMEN

With advancements in nanotechnology and innovative materials, Graphene Oxide nanoparticles (GONP) have attracted lots of attention among the diverse types of nanomaterials owing to their distinctive physicochemical characteristics. However, the usage at scientific and industrial level has also raised concern to their toxicological interaction with biological system. Understanding these interactions is crucial for developing guidelines and recommendations for applications of GONP in various sectors, like biomedicine and environmental technologies. This review offers crucial insights and an in-depth analysis to the biological processes associated with GONP immunotoxicity with multiple cell lines including human whole blood cultures, dendritic cells, macrophages, and multiple cancer cell lines. The complicated interactions between graphene oxide nanoparticles and the immune system, are highlighted in this work, which reveals a range of immunotoxic consequences like inflammation, immunosuppression, immunostimulation, hypersensitivity, autoimmunity, and cellular malfunction. Moreover, the immunotoxic effects are also highlighted with respect to in vivo models like mice and zebrafish, insighting GO Nanoparticles' cytotoxicity. The study provides invaluable review for researchers, policymakers, and industrialist to understand and exploit the beneficial applications of GONP with a controlled measure to human health and the environment.


Asunto(s)
Grafito , Grafito/toxicidad , Grafito/química , Humanos , Animales , Nanopartículas , Sistema Inmunológico/efectos de los fármacos
19.
Microb Pathog ; 192: 106687, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38750773

RESUMEN

Bovine mastitis (BM) is the most common bacterial mediated inflammatory disease in the dairy cattle that causes huge economic loss to the dairy industry due to decreased milk quality and quantity. Milk is the essential food in the human diet, and rich in crucial nutrients that helps in lowering the risk of diseases like hypertension, cardiovascular diseases and type 2 diabetes. The main causative agents of the disease include various gram negative, and positive bacteria, along with other risk factors such as udder shape, age, genetic, and environmental factors also contributes much for the disease. Currently, antibiotics, immunotherapy, probiotics, dry cow, and lactation therapy are commonly recommended for BM. However, these treatments can only decrease the rise of new cases but can't eliminate the causative agents, and they also exhibit several limitations. Hence, there is an urgent need of a potential source that can generate a typical and ideal treatment to overcome the limitations and eliminate the pathogens. Among the various sources, medicinal plants and its derived products always play a significant role in drug discovery against several diseases. In addition, they are also known for its low toxicity and minimum resistance features. Therefore, plants and its compounds that possess anti-inflammatory and anti-bacterial properties can serve better in bovine mastitis. In addition, the plants that are serving as a food source and possessing pharmacological properties can act even better in bovine mastitis. Hence, in this evidence-based study, we particularly review the dietary medicinal plants and derived products that are proven for anti-inflammatory and anti-bacterial effects. Moreover, the role of each dietary plant and its compounds along with possible role in the management of bovine mastitis are delineated. In this way, this article serves as a standalone source for the researchers working in this area to help in the management of BM.


Asunto(s)
Antibacterianos , Antiinflamatorios , Mastitis Bovina , Plantas Medicinales , Animales , Bovinos , Mastitis Bovina/microbiología , Mastitis Bovina/tratamiento farmacológico , Mastitis Bovina/prevención & control , Plantas Medicinales/química , Antiinflamatorios/farmacología , Femenino , Antibacterianos/farmacología , Humanos , Leche , Dieta/veterinaria , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico
20.
Bioorg Chem ; 149: 107473, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38820940

RESUMEN

In silico approaches have been employed to design a new series of benzimidazole-containing sulphonamide derivatives and qualified compounds have been synthesized to analyze their potential as antimicrobial agents. Antibacterial screening of all synthesized compounds was done using the broth microdilution method against several human pathogenic bacteria, viz. Gram-positive bacteria [B. cerus (NCIN-2156), B. subtilis (ATCC-6051), S. aureus (NCIM-2079)] and Gram-negative bacteria [P. aeruginosa (NCIM-2036), E. coli (NCIM-2065), and a drug-resistant strain of E. coli (U-621)], and the compounds presented admirable MIC values, ranging between 100-1.56 µg/mL. The combinatorial analysis showed the magnificent inhibitory efficiency of the tested compounds, acquired equipotent to ten-fold more potency compared to original MIC values. An immense synergistic effect was exhibited by the compounds during combination studies with reference drugs chloramphenicol and sulfamethoxazole was presented as fractional inhibitory concentration (∑FIC). Enzyme inhibition studies of all synthesized compounds were done by using peptidyl transferase and dihydropteroate synthase enzymes isolated from E. coli and S. aureus and each of the compound presented the admirable IC50 values, where the lead compound 3 bound to peptidyl transferase (of S. aureus with IC50 363.51 ± 2.54 µM and E. coli IC50 1.04 ± 0.08 µM) & dihydropteroate synthase (of S. aureus IC50 3.51 ± 0.82 µM and E. coli IC50 2.77 ± 0.65 µM), might account for the antimicrobial effect, exhibited excellent inhibition potential. Antifungal screening was also performed employing food poisoning methods against several pathogenic fungal species, viz A. flavus, F. oxysporum, A. niger, and A. brassicae. The obtained result indicated that few compounds can prove to be a potent drug regimen against dreaded MDR strains of microbes. Structural activity relationship (SAR) analysis and docking studies reveal that the presence of electron-withdrawing, polar, and more lipophilic substituents positively favor the antibacterial activity, whereas, electron-withdrawing, more polar, and hydrophilic substituents favor the antifungal activities. A robust coherence has been found in in-silico and in-vitro biological screening results of the compounds.


Asunto(s)
Antibacterianos , Bencimidazoles , Diseño de Fármacos , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Sulfonamidas , Bencimidazoles/farmacología , Bencimidazoles/química , Bencimidazoles/síntesis química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Relación Estructura-Actividad , Sulfonamidas/química , Sulfonamidas/farmacología , Sulfonamidas/síntesis química , Estructura Molecular , Teoría Funcional de la Densidad , Relación Dosis-Respuesta a Droga , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Dihidropteroato Sintasa/antagonistas & inhibidores , Dihidropteroato Sintasa/metabolismo , Humanos , Antifúngicos/farmacología , Antifúngicos/síntesis química , Antifúngicos/química , Escherichia coli/efectos de los fármacos
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